Abstracts

Rationale: Glutamic acid decarboxylase (GAD65) antibody-associated epilepsy (GAD65AE) is increasingly recognized as a distinct etiology for epilepsy. The heterogeneity of its clinical and neurophysiological features and variable responses to treatment make GAD65AE challenging to diagnose and treat. Reporting cases of this overall rare condition can contribute to the growing body of knowledge and hopefully stimulate further studies to understand this condition and improve patient care.

Methods: Case 1 is a 43-year-old man with seizure onset at age 30. Case 2 is a 25-year-old woman with seizure onset at age 22. Case 3 is a 64 years old woman with hypertension and type II diabetes who presented with seizures starting at age 64.

Results: Seizures were subacute onset in all three cases. Case 1 presented with psychic aura followed by behavior arrest with impairment of awareness. EEG showed bitemporal interictal discharges (IEDs) and bitemporal onset subclinical and clinical seizures. Initial MRI was unremarkable, but right mesial temporal sclerosis was observed one year later. Case 2 presented with confusion, followed by the right version and generalized tonic-clonic seizures. EEG showed left temporal IEDs and left temporal onset subclinical and clinical seizures. Case 3 presented with tongue and left facial dystonic/clonic movements with preserved awareness. EEG showed bifrontal IEDs but no recognizable ictal pattern due to muscle artifacts. MRI for both cases 2 and 3 were unremarkable. High titer GAD65 antibodies were detected in serum ( > 250 nmol/L) and CSF in all cases. Case 2 also had coexisting thyroid peroxidase antibodies (TPO 15.2 KU/ml) in serum. Prolonged ambulatory EEG monitoring (2-3 days duration) was utilized every 3-6 months to evaluate seizure frequency and response to therapy. Subclinical seizures were detected on multiple ambulatory EEG in case 1 and case 2, aiding the treatment plan. Despite multiple antiseizure medications (ASMs) and immunomodulatory therapies such as steroids, intravenous immunoglobulin (IVIG) (except case 3 due to patient’s preference of bloodless) and rituximab, patients continued to experience weekly seizures. They also developed comorbidities, such as fatigue, headaches, mood disturbances, cognitive decline, peripheral neuropathy, and balance issues. Case 1 eventually discontinued all immunomodulatory therapy due to lack of efficacy. Epilepsy surgeries were either declined by the patients or deemed unsuitable due to the progression from focal to bihemispheric/multifocal seizures.

Conclusions: GAD65 antibody testing should be considered in all adult patients with new-onset epilepsy without other identifiable etiologies. The heterogeneity in clinical presentation and electrographic features of GAD65AE complicates early diagnosis. Treating patients with GAD65AE is highly challenging and multicenter studies are essential to develop more effective treatment options. Additionally, prolonged EEG monitoring is crucial for evaluating seizure frequency and treatment response.

Funding: none